title: Diabetic mouse model of orthopaedic implant-related Staphylococcus aureus infection.
abstract: BACKGROUND
  Periprosthetic bacterial infections represent one of the most challenging orthopaedic complications that often require implant removal and surgical debridement and carry high social and economical costs. Diabetes is one of the most relevant risk factors of implant-related infection and its clinical occurrence is growing worldwide. The aim of the present study was to test a model of implant-related infection in the diabetic mouse, with a view to allow further investigation on the relative efficacy of prevention and treatment options in diabetic and non-diabetic individuals.
  
  
  METHODS
  A cohort of diabetic NOD/ShiLtJ mice was compared with non-diabetic CD1 mice as an in vivo model of S. aureus orthopaedic infection of bone and soft tissues after femur intramedullary pin implantation. We tested control and infected groups with 1×10(3) colony-forming units of S. aureus ATCC 25923 strain injected in the implant site. At 4 weeks post-inoculation, host response to infection, microbial biofilm formation, and bone damage were assessed by traditional diagnostic parameters (bacterial culture, C-reactive protein and white blood cell count), histological analysis and imaging techniques (micro computed tomography and scanning electron microscopy).
  
  
  RESULTS
  Unlike the controls and the CD1 mice, all the diabetic mice challenged with a single inoculum of S. aureus displayed severe osteomyelitic changes around the implant.
  
  
  CONCLUSIONS
  Our findings demonstrate for the first time that the diabetic mouse can be successfully used in a model of orthopaedic implant-related infection. Furthermore, the same bacteria inoculum induced periprosthetic infection in all the diabetic mice but not in the controls. This animal model of implant-related infection in diabetes may be a useful tool to test in vivo treatments in diabetic and non-diabetic individuals.
authors.affiliation: Cell and Tissue Engineering Laboratory, Gruppo Ospedaliero San Donato Foundation, Milan, Italy. arianna.lovati@grupposandonato.it
authors.forename: Arianna B
authors.initials: AB
authors.lastname: Lovati
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Drago
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Monti
authors.forename: Elena
authors.initials: E
authors.lastname: De Vecchi
authors.forename: Sara
authors.initials: S
authors.lastname: Previdi
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Banfi
authors.forename: Carlo L
authors.initials: CL
authors.lastname: Romanò
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D018441:Biofilms / Q000254:growth & development; D002097:C-Reactive Protein / Q000378:metabolism; D015169:Colony Count, Microbial; D003922:Diabetes Mellitus, Type 1 / Q000150:complications*; D004195:Disease Models, Animal; D005269:Femur / Q000601:surgery; D054884:Host-Pathogen Interactions; D006801:Humans; D051379:Mice; D016688:Mice, Inbred NOD; D008855:Microscopy, Electron, Scanning; D019637:Orthopedic Procedures / Q000009:adverse effects; D019736:Prostheses and Implants / Q000009:adverse effects; D016459:Prosthesis-Related Infections / Q000175:diagnosis* / Q000209:etiology / Q000382:microbiology; D013203:Staphylococcal Infections / Q000175:diagnosis* / Q000209:etiology / Q000382:microbiology; D013211:Staphylococcus aureus / Q000254:growth & development* / Q000502:physiology / Q000648:ultrastructure; D055114:X-Ray Microtomography
chemical_list: D002097:C-Reactive Protein